Biparametric (bp) and multiparametric (mp) magnetic resonance imaging (MRI) approach to prostate cancer disease: a narrative review of current debate on dynamic contrast enhancement

Prostate cancer is the most common malignancy in male population. Over the last few years, magnetic resonance imaging (MRI) has proved to be a robust clinical tool for identification and staging of clinically significant prostate cancer. Though suggestions by the European Society of Urogenital Radiology to use complete multiparametric (mp) T2-weighted/diffusion weighted imaging (DWI)/dynamic contrast enhancement (DCE) acquisition for all prostate MRI examinations, the real advantage of functional DCE remains a matter of debate. Recent studies demonstrate that biparametric (bp) and mp approaches have similar accuracy, but controversial evidences remain, and the specific potential benefits of contrast medium administration are still poorly discussed in literature. The bp approach is in fact sufficient in most cases to adequately identify a negative test, or to accurately define the degree of aggressiveness of a lesion, especially if larger or with major characteristics of malignancy. This feature would give the DCE a secondary role, probably limited to a second evaluation of the lesion location, for detecting small cancer or in case of controversy. However, DCE has proved to increase the sensitivity of prostate MRI, though a less specificity. Therefore, an appropriate decision algorithm is needed to standardize the MRI approach. Aim of this review study was to provide a schematic description of bpMRI and mpMRI approaches in the study of prostatic anatomy, focusing on comparative validity and current DCE application. Additional theoretical considerations on prostate MRI are provided

Tracking flowpaths in a complex karst system through tracer test and hydrogeochemical monitoring: Implications for groundwater protection (Gran Sasso, Italy)

Groundwater in karst aquifers is frequently tapped for drinking purposes, due to frequent huge volumes of resources. Unfortunately, vulnerability of these aquifers can be high, due to possible fast transfer of recharge water on springs by the karst network. On Gran Sasso Mountain regional aquifer, several springs are subjected to drinking withdrawal and an updated evaluation of their potential is now a fundamental issue to be considered, facing climate change effects, which reflect on variation of discharge regimen and values. To distinguish between different contribution of spring recharge, a tracer test has been carried out on the Vitella d’Oro spring, fed both by the regional aquifer and by a local system exposed to karst features developed in the Rigopiano Conglomerates formation. Thanks to hydrogeological, hydrogeochemical and isotopic data, a conceptual model of spring recharge has been proposed and subsequently validated by the tracer test results. All information confirms the superimposition on the regional base flow, by a relevant contribution of the karst network, influencing the spring discharge in recharge periods. In detail, a fast flow component is responsible for discharge peaks and frequently of turbidity events, having a mean velocity ranging from 30 to 70 m/h in the aquifer. Besides of this fast flow, an additional aliquot of the recharge is due to the same local aquifer, but slower flow clearly identifiable by hydrochemistry and isotopic data. Thanks to these findings, a renewed manage- ment of the spring has been suggested, considering the different degrees of aquifer vulnerability (turbidity occurrence) directly related to the discharge regimen

Acute Surgical Pulmonary Embolectomy: A 9-Year Retrospective Analysis

Acute pulmonary embolism is a substantial cause of morbidity and death. Although the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines recommend surgical pulmonary embolectomy in patients with acute pulmonary embolism associated with hypotension, there are few reports of 30-day mortality rates. We performed a retrospective review of acute pulmonary embolectomy procedures performed in 96 consecutive patients who had severe, globally hypokinetic right ventricular dysfunction as determined by transthoracic echocardiography. Data on patients who were treated from January 2003 through December 2011 were derived from health system databases of the New York State Cardiac Surgery Reporting System and the Society of Thoracic Surgeons. The data represent procedures performed at 3 tertiary care facilities within a large health system operating in the New York City metropolitan area. The overall 30-day mortality rate was 4.2%. Most patients (68 [73.9%]) were discharged home or to rehabilitation facilities (23 [25%]). Hemodynamically stable patients with severe, globally hypokinetic right ventricular dysfunction had a 30-day mortality rate of 1.4%, with a postoperative mean length of stay of 9.1 days. Comparable findings for hemodynamically unstable patients were 12.5% and 13.4 days, respectively. Acute pulmonary embolectomy can be a viable procedure for patients with severe, globally hypokinetic right ventricular dysfunction, with or without hemodynamic compromise; however, caution is warranted. Our outcomes might be dependent upon institutional capability, experience, surgical ability, and careful patient selection

The Medical Impact of Hepatitis D Virus Infection in Natives and Immigrants: The Italian Paradigm

Background and Aim: Ongoing migratory flows are reconstituting the hepatitis D virus (HDV) reservoir in Italy. We aimed to characterise the current clinical and virologic features of HDV infection in both native Italians and migrants. Methods: We enrolled 515 hepatitis B surface antigen (HBsAg)-positive patients with detectable anti-HDV antibodies from 32 Italian centres between August 2022 and July 2024; all patients underwent centralised virologic assessment. Results: Overall, 432 out of 515 (83.9%) patients were HDV-RNA-positive (4.39, 1.30–5.82 Log IU/mL; 99.0% HDV genotype-1). HDV-RNA levels correlated with ALT (rs = 0575, 0.514–0.630) and hepatitis B core-related antigen (rs = 0.521, 0.455–0.581). Native Italians (n = 317; 61.6%) were older than migrants (n = 198; 38.4%) (median age: 60, 55–65 vs. 46, 39–54 years; p < 0.001) and were more frequently male (68.1% vs. 49.5%; p < 0.001), with a higher prevalence of liver cirrhosis (70.3% vs. 50.5%; p < 0.001) and hepatocellular carcinoma (14.8% vs. 0.5%; p < 0.001). Among Italians, 223 (70.3%) had liver cirrhosis, 46 (14.5%) had chronic hepatitis D (CHD) without cirrhosis and 48 (15.1%) exhibited inactive/minimal disease with low viremia (≤ 3 Log IU/mL). Among migrants, 100 (50.5%) had liver cirrhosis, 58 (29.3%) had CHD and 40 (20.2%) showed inactive/minimal disease with low viremia (≤ 3 Log IU/mL). Conclusions: The current clinical landscape of chronic HDV infections in Italy is heterogeneous, changing the perspective of CHD as uniformly severe; although cirrhosis remains common, a substantial proportion of both native Italians and migrants present with milder forms of disease

Clinicopathological Significance and Prognostic Value of DNA Methyltransferase 1, 3a, and 3b Expressions in Sporadic Epithelial Ovarian Cancer

Altered DNA methylation of tumor suppressor gene promoters plays a role in human carcinogenesis and DNA methyltransferases (DNMTs) are responsible for it. This study aimed to determine aberrant expression of DNMT1, DNMT3a, and DNMT3b in benign and malignant ovarian tumor tissues for their association with clinicopathological significance and prognostic value. A total of 142 ovarian cancers and 44 benign ovarian tumors were recruited for immunohistochemical analysis of their expression. The data showed that expression of DNMT1, DNMT3a, and DNMT3b was observed in 76 (53.5%), 92 (64.8%) and 79 (55.6%) of 142 cases of ovarian cancer tissues, respectively. Of the serious tumors, DNMT3a protein expression was significantly higher than that in benign tumor samples (P = 0.001); DNMT3b was marginally significant down regulated in ovarian cancers compared to that of the benign tumors (P = 0.054); DNMT1 expression has no statistical difference between ovarian cancers and benign tumor tissues (P = 0.837). Of the mucious tumors, the expression of DNMT3a, DNMT3b, and DNMT1 was not different between malignant and benign tumors. Moreover, DNMT1 expression was associated with DNMT3b expression (P = 0.020, r = 0.195). DNMT1 expression was associated with age of the patients, menopause status, and tumor localization, while DNMT3a expression was associated with histological types and serum CA125 levels and DNMT3b expression was associated with lymph node metastasis. In addition, patients with DNMT1 or DNMT3b expression had a trend of better survival than those with negative expression. Co-expression of DNMT1 and DNMT3b was significantly associated with better overall survival (P = 0.014). The data from this study provided the first evidence for differential expression of DNMTs proteins in ovarian cancer tissues and their associations with clinicopathological and survival data in sporadic ovarian cancer patients

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol

BACKGROUND: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. METHODS: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0–2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). FINDINGS: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86–107) in the abiraterone trial and 72 months (61–74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8–86·9) in the abiraterone group versus 45·7 months (41·6–52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53–0·73]; p<0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9–81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3–59·0) in the standard of care group (HR 0·65 [0·55–0·77]; p<0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83–1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3–5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial). INTERPRETATION: Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years. FUNDING: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas

Chemoprevention of Human Cancer:A Reasonable Strategy?

The field of chemoprevention of cancer in humans is at a teenage level of maturity. There is anticipation and energy, and some promising results have come in, but it's unclear whether the entire enterprise is worth the effort. Reflecting on the status of the organism and where we are in its developmental history is therefore an important exercise at this time. Empirical and philosophical perspectives are offered for several key questions: Why prevent Cancer? What is the preclinical evidence that chemoprevention of cancer in humans should work? What is the clinical evidence that chemoprevention agents work? What is the clinical evidence that chemoprevention agent don't work? What is the status of ongoing randomized phase III/IV chemoprevention trials? The answers to each of these questions provide a part of the scaffold for a logical platform for the launching of the chemoprevention imperative as an integral part of our approach to the overall management of human cancer